Advanced Ovarian Cancer -- A Clinical Context Report

CHARLES BANKHEAD: I'm Charles Bankhead of MedPage Today. Welcome to this episode of Clinical Context: Advanced Ovarian Cancer. This is the first of two programs that will address the current state of treating advanced ovarian cancer with particular emphasis on the integration of targeted therapies.

Joining me today is Dr. Justin Chura of Crozer-Chester Medical Center in Upland, Pennsylvania. Dr. Chura is also a spokesperson on clinical matters for the Society of Gynecologic Oncology.

Thank you for joining us today, Dr. Chura.

JUSTIN CHURA, MD: My pleasure to be here, thank you.

BANKHEAD: Could we start out by addressing a little bit the scope of the problem? Why would we be talking about advanced ovarian cancer as opposed to early-stage cancer, which most people would hope that the disease could be detected early, but I guess that's not the case?

CHURA: That's correct. One of the problems with ovarian cancer is that presently we do not have adequate screening tests to detect the disease at an early stage, so most patients, 75%, are stage III or IV when they're diagnosed because of the lack of screening. So we don't have the equivalent [of a] mammogram for detecting breast cancer, colonoscopy for detecting colon cancer; we don't have that for ovarian cancer patients. Thus the majority of the patients present at an advanced stage, stage III or IV, and when that's the case, the patient is already behind the eight ball, and it makes it a much more difficult process or difficult disease to treat and cure. It's not to say we can't cure some of those patients, but when we start at an advanced stage, the likelihood of cure is much lower, and that's for any cancer in general.

BANKHEAD: According to the National Comprehensive Cancer Network, which establishes recommended guidelines for treating a wide variety of cancers, what is the beginning approach for treating advanced ovarian cancer with systemic therapy?

CHURA: So the hallmarks of treatment for ovarian cancer are both surgery and chemotherapy, and in most circumstances we proceed with surgery as our first starting point. The goal of surgery is to remove all visible cancer deposits that one can find in the abdominal pelvic cavity at that time.

So these can be fairly extensive and vigorous surgeries in terms of the amount of dissection that occurs, in terms of the length of the procedures. But it's been demonstrated that the ability to remove all cancer deposits that are seen, or at least all cancer deposits such that one's not leaving any large nodules, nothing larger than a centimeter, improves our patients' outcomes.

So as we said earlier, most patients are stage III or IV when they walk through the physician's door; we can't change that. What we can change as GYN oncologists is the success of our surgery in terms of setting the patient up for the best possible response afterwards, and that includes a surgery that is aimed at removing all tumor deposits one can find.

Following surgery is then systemic therapy, which you're asking about, which is chemotherapy. And for patients with stage III disease, the systemic therapy option that is preferred at this time is a combination of intraperitoneal and intravenous chemotherapy.

BANKHEAD: What are the preferred agents for treating advanced ovarian cancer?

CHURA: The hallmark agents are platinum and taxane-based chemotherapy. So with an intraperitoneal regimen, that's cisplatinum and paclitaxel. If it's just an intravenous regimen, it would be carboplatinum and paclitaxel.

BANKHEAD: Could you discuss a little bit about the importance of intraperitoneal therapy and some of the difficulties that have been encountered in using it?

CHURA: Certainly. So the benefit of intraperitoneal chemotherapy to the patient is quite profound. When studied in a randomized trial where patients were randomized to either conventional intravenous chemotherapy after surgery or a combination of intraperitoneal and intravenous, the patients in the intraperitoneal arm had a 16-month survival advantage. That is a striking survival advantage for these patients when dealing with such a fatal disease.

So that survival advantage is very significant, but it does come at an increased cost for the patient. The short-term side effects are more significant, or the short-term toxicities of the regimen. That can include a higher risk of neuropathy or numbness and tingling in the fingers or toes. That can include problems with the catheter itself that is used to administer the chemotherapy, such as blockage of the catheter or infections related to the catheter, and pain from the administration of that chemotherapy.

That being said, when -- in our most recent gynecologic oncology group study that looked at this regimen, we also did study quality of life. And after all the treatment was complete, quality of life was the same for both groups of patients. During the treatment the patients receiving the intraperitoneal chemotherapy did have a slightly worse quality of life, but afterwards that was balanced out.

BANKHEAD: What are some additional recommended or possible therapies, aside from the classic platinum/taxane combination? I believe that there are other regimens that can be used. What are they, and when might they come into play?

CHURA: Certainly. So other regimens besides platinum/taxane-based could include the combination of platinum with the drug gemcitabine, or a combination of platinum with topotecan, or platinum with liposomal doxorubicin, so those are all other viable options for the treatment of advanced-stage ovarian cancer. Those other regimens might be used if, for example, one is worried about worsening of neuropathy, numbness, or tingling in the fingers or toes in the patient. And suppose this patient is a pianist, and so numbness and tingling in her fingers would ruin her career potentially. So that's a patient for whom we might alter the regimen, where we'll select drugs that will not have a neuropathy type side effect for her.

BANKHEAD: In the treatment of advanced ovarian cancer, women not uncommonly have one or more relapses that require treatment. Could you comment on the approach to treating relapse or recurrent disease, and also with emphasis on what has come to be known as platinum sensitivity?

CHURA: Certainly. So when a patient recurs, it depends upon where she is in the course of her disease process in terms of how we treat her at that time. If it has been a long interval of remission, and if there's only one or two isolated areas of recurrent cancer, one may consider surgery as a second procedure or a second surgery before proceeding again with systemic therapy, so this can be called a secondary cytoreduction surgery. That procedure is best suited for patients who have what's called a good performance status and for patients who do not have multiple sites of disease.

Following that surgery then leaves us with, again, the option of more systemic therapy. And if a patient is deemed what's called platinum-sensitive, that means that their remission has been greater than six months, and one would consider treating with a platinum-based regimen again. That can include carboplatinum plus liposomal doxorubicin; that could include carboplatinum plus paclitaxel, or carboplatinum plus gemcitabine.

If a patient is platinum-resistant, and by definition that's less than a six-month remission, then we typically treat with a single-agent therapy such as liposomal doxorubicin, gemcitabine, topotecan, paclitaxel given in a weekly fashion, or other agents such as bevacizumab, aromatase inhibitors, or etoposide.

It should also be noted that the platinum-sensitive, platinum-resistant definition is arbitrary in the sense that we pick six months as a line in the sand, if you will. But clearly the patients whose remission is longer are the patients who definitely will have a better prognosis going forward.

BANKHEAD: As the NCCN noted in their most recent guidelines, there is some emerging data involving the use of targeted therapies; specifically, bevacizumab. Could you comment on what is known about the use of bevacizumab in advanced ovarian cancer at this point?

CHURA: Certainly. So bevacizumab has been studied both in patients with recurrent cancer, and it's been studied as part of the treatment regimen for patients in their first course of therapy, so we have two separate populations. And for patients with recurring cancer, we know that it is an active drug; that it can arrest the disease process. It does not typically lead to a complete -- what's called a complete response, but it might achieve a partial response or stabilization of the disease process.

The more recent studies that have been done have looked at bevacizumab as part of front-line therapy. In that circumstance, this was a trial that studied a combination of paclitaxel and carboplatinum plus bevacizumab, and it looked at bevacizumab as what's called maintenance therapy following the completion of the first chemotherapy. So this was actually a three-arm trial, where the first arm received carboplatinum and paclitaxel; the second arm received carboplatinum, paclitaxel, and bevacizumab; and then the third arm received carboplatinum, paclitaxel, and bevacizumab, but they continued on the bevacizumab for what's called maintenance therapy. In that group of patients there was an improvement in progression-free survival. In the study, there was not a difference in the overall survival among the groups, but there was a significant difference in progression-free survival for patients who received maintenance chemotherapy with bevacizumab.

BANKHEAD: One of the ongoing debates about management of advanced ovarian cancer involves monitoring patients, particularly with the use of the CA125 antigen. What are your thoughts about the current role of CA125 and whether there are other markers that might be useful in following the progress of patients?

CHURA: So certainly CA125 can be very useful to monitor a patient's status in addition to a history and physical exam that's done. The CA125 can often detect a recurrence of cancer before the patient has symptoms or before there's an abnormality on clinical examination.

The issue with this monitoring is that it has not been shown that an earlier detection improves our patients' outcome, so there is some controversy there in terms of the role of CA125 monitoring for patients who have completed all their therapy and have achieved a complete response; that's very much an individualized decision between the patient and physician.

That being said, because of the ability of the assay to detect disease often before it's identified on exam or identified on any type of imaging studies, many patients do elect to undergo monitoring with the CA125 assay.

CHURA: There are other biomarkers; HE4 is one that had been looked at in terms of monitoring for recurring disease. They've also looked at some of these biomarkers for looking at early detection. That being said, CA125 is still sort of the cornerstone of surveillance if one is going to do surveillance with blood testing.

BANKHEAD: Do you have any additional comments about where the field of gynecologic oncology may be headed with respect to treating advanced ovarian cancer?

CHURA: Certainly. I think that there has been a paradigm shift in our surgical treatment that has been evolving over years. Even in my career, we've seen a shift in surgery being considered what's called optimal if there's no tumor deposit left behind greater than two centimeters, to optimal then being defined as no tumor deposit less than a centimeter, to now where our surgical goal is to remove all disease that we can find.

So there has been a significant shift in the surgical paradigm. In addition, the chemotherapy is now looking at more and more targeted agents, which tend to have less side effects or toxicities compared to the conventional chemotherapy. Bevacizumab, as we've discussed, is the one that has had the most amount of research to date and is the one that has been used both in patients with new diagnosis of ovarian cancer as well as with a diagnosis of recurrence, but other agents are also being studied.

I think the other focus of our research efforts for our patients is early detection. If we could detect this disease at an early stage, we would make a significant improvement in our patients' outcomes; there's no doubt about that.

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.